The present invention relates to a composition and method for preventing or inhibiting biofilm formation on a surface, particularly an abiotic surface, using the composition.
Pseudomonas is a gram negative bacteria which is a notorious cause of nosocomial or hospital acquired infections. It is a significant pathogen in several clinical settings, especially in immunocompromised patients. Psuedomonas aeruginosa is the most common disease causing Pseudomonas species.
Pseudomonas aeruginosa is an effective and common opportunistic pathogen of humans, causing serious infections in cystic fibrosis, intensive care, burn, and immuno-compromised patients (Bodey et al., 1983; Pier, 1985; Costerton, 2001). Initial binding of the bacterium to an abiotic or a cellular substratum is considered by many to be the initial stage of colonization for both biofilm formation (Watnick and Kolter, 2000) and initiation of an infection (Beachey, 1981). Recently, P. aeruginosa biofilms have been implicated during chronic infection of cystic fibrosis patients (O'Toole et al., 2000; Singh et al., 2000). In addition to chronic infection, P. aeruginosa biofilms contribute to morbidity of patients with medical implants including catheters (Kumon et al., 1997; Khaled et al., 2001), prosthetics (McNeil et al., 2001) and stainless steel implants (Traverso et al., 2005).
Stainless steel is widely used, particularly in the food sector, and commonly used in the hospital environment and in medical devices (Hood et al., 1997). P. aeruginosa readily binds to stainless steel (Stanley, 1983; VanHaecke et al., 1990) to form biofilms (Leake et al., 1982; Blenkinsopp et al., 1992; Johansen et al., 1997). P. aeruginosa biofilms on stainless steel surfaces can serve as a significant hospital reservoir for the infection of susceptible patients (Tredget et al., 1992). Type IV pili are essential for the normal development of P. aeruginosa biofilms as mutants lacking the ability to form pili are unable to develop past the microcolony stage in static or flow biofilm systems (O'Toole and Kolter, 1998; Klausen et al., 2003).
Type IV pili are composed of a single pilin subunit, PilA, and are assembled into long polar surface appendages (Folkhard et al., 1981). This assembly process ensures that the receptor binding domain is only located at the tip of the pilus (Lee et al., 1994). The pilus-associated epithelial cell receptor binding domain is encoded in residues 128-144 of the C-terminal region of PilA, the pilin structural protein (Irvin et al., 1989a). This terminal binding domain specifically recognizes GalNAc-β-D-(1,4)-Gal moieties of asialo-GM1 as a minimal receptor (Sheth et al., 1994). Adherence to this receptor is specific and can be inhibited by a synthetic receptor binding domain, PAK(128-144)ox, or by synthetic GalNAc-β-D-(1,4)-Gal (Sheth et al., 1994; Wong et al., 1995; Schweizer et al, 1998).
Although it has been recognized that biofilms are directly responsible for a large number of problematic diseases resulting in high mortality and morbidity and for massive losses in the economy by causing fouling of pipes, ships, and heat treatment equipment, prevention or modulation of biofilm formation has been extremely challenging. The currently available methods rely on extreme measures such as releasable antibiotics, colloidal silver deposition, laser ablation, and electric field pulses.
Accordingly, there is a need for a new composition and method for preventing or inhibiting biofilm formation on both biotic and abiotic surfaces. Towards this end, the present inventors discovered a composition which binds to an abiotic surface (e.g. steel) with high affinity and prevents binding of a variety of P. aeruginosa strains to the surface. Thus, the invention provides a new means of preventing or inhibiting biofilm formation. The advantage of the invention will become apparent by the following description.